The National Cancer Institute estimates 1,334,100 new cancer cases are expected to be diagnosed in the United States during 2003 and 556,500 people will die from the disease. Prostate and lung cancers are the leading cause of death in men while breast cancer and lung cancer are the leading cause of death in women. It is also estimated that 8.9 million Americans with a history of cancer were alive in 1999. Worldwide the mortality statistics are more dismal due, in part, to the lack of early diagnosis opportunities available in developing countries.
Despite advances in cancer treatment strategies, lack of efficacy and/or significant side effects due to the toxicity of currently used chemotherapeutic agents remain a problem. Drug toxicity can be severe enough to result in life threatening situations requiring administration of drugs to counteract side effects, and may result in the reduction or discontinuation of the chemotherapeutic agent. One of the major limitations to clinical use of cancer therapeutic agents is the development of resistance to the treatment. These drawbacks to current therapies impact negatively on the patient's treatment and quality of life and exemplify the need for new anticancer therapies.
The development of tumor malignancy, and particular, the progression from a primary tumor to a metastatic cancer, may involve alterations in a tumor cell's ability to adhere and communicate with neighboring cells and with its extracellular environment. Intercellular adhesion of epithelial cells during embryonic development and in adult tissues is mediated by the protein E-cadherin. E-cadherin is also implicated in the phenotypic transformation observed in epithelial tumors during their progression into invasive tumors. Expression of the protein E-cadherin may be reduced or abolished in the process of tumor cell invasion and this loss is associated with the progression to tumor malignancy. The modification of E-cadherin has also been associated with de-differentiation and greater aggressiveness of tumors (Takeichi 1993; Birchmeier and Behrens 1994) and has been implicated in the transition from adenomas to invasive carcinomas (Perl, Wilgenbus et al. 1998). These observations support the suggestion that the E-cadherin gene is a tumor invasion suppressor gene (Llorens, Rodrigo et al. 1998).
It would therefore be desirable to develop a therapy that would prevent or suppress the progression of a tumor, e.g., solid tumor, to an invasive or metastatic state, through a mechanism that acts to maintain expression of the protein E-cadherin in cancer cells.
It would be further desirable to develop a therapy that can be used in conjunction with conventional chemotherapeutic agents to control the growth and spread of cancer cells in a subject.